Abstract | BACKGROUND & OBJECTIVE: METHODS: The CK2 holoenzyme composed of alphao and beta subunits was recombined in vitro. Subsequently, CK2 was treated with mitoxantrone at various concentrations, followed by addition of reacting liquid containing [gamma-32P] ATP. CK2 activity was measured by detecting the radioactivity of 32P transferred onto the substrates of CK2. The effect of mitoxantrone on the proliferation of HL-60 cells was detected by the trypan blue dye exclusion assay; the changes in the cell cycle were analyzed by flow cytometry (FCM); apoptosis was analyzed by FCM and DNA agarose gel electrophoresis; effects of the drugs on the intrinsic CK2 activity were measured by a specific CK2 peptide substrate. RESULTS:
Mitoxantrone strongly inhibited the holoenzyme activity of recombinant human protein kinase CK2 (IC50=0.66 micromol/L). The inhibition of CKZ by mitoxantrone was competitive with respect to ATP (Ki 0.25 micromol/L) and mostly non-competitive with respect to casein (Ki 0.66 micromol/L). Mitoxantrone exerted strong cytotoxicity to HL-60 cells. When treated with 0.1 micromol/L mitoxantrone for 12 h, the apoptotic rate of HL-60 cells was 9.3%. Mitoxantrone did not affect intracellular CK2 activity. CONCLUSIONS:
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Authors | Chun-Mei Li, Xin-Guang Liu, Xiao-Cong Lin, Xiao-Wen Chen, Nian-Ci Liang |
Journal | Ai zheng = Aizheng = Chinese journal of cancer
(Ai Zheng)
Vol. 27
Issue 8
Pg. 809-15
(Aug 2008)
China |
PMID | 18710613
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Holoenzymes
- Recombinant Proteins
- Mitoxantrone
- Casein Kinase II
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Casein Kinase II
(antagonists & inhibitors, metabolism)
- Cell Cycle
(drug effects)
- DNA Fragmentation
(drug effects)
- Enzyme Activation
(drug effects)
- HL-60 Cells
- Holoenzymes
(metabolism)
- Humans
- Mitoxantrone
(pharmacology)
- Recombinant Proteins
(metabolism)
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